High Resolution MRI of Myocardial Deformation (competing renewal application). In the first funding period of this grant we have developed novel imaging and analysis techniques for acquiring measurements of myocardial strain with unprecedented spatial resolution over the entire left ventricle. These methods have been rigorously optimized and validated with simulations and experiments. The methods which were developed to achieve high spatial resolution have lead immediately to robust clinical protocols that are now being used to characterize the normal and ischemic human heart. In this next phase of the project we plan to extend our high spatial resolution techniques into high temporal resolution techniques with the goal to measure the relationship between ectopic electrical activation and mechanical contraction in the normal, ischemic, [and failing] heart. Our preliminary data show that we can resolve a "pulse" of myocardial contraction that emanates from a pacing site, travels around the left ventricle, and converges on the opposite wall of the heart. This propagation occurs during the l50ms after the pacing stimulation and the velocity is direction dependent. We plan to investigate the interaction of the mechanical and electrical properties of myocardium by pursuing the following specific aims: (1) Develop novel imaging sequences with the spatial and temporal resolution to measure the propagation of mechanical contraction in 3 dimensions during ventricular pacing. (2) Develop image analysis methods to incorporate new tagging patterns into the high temporal resolution estimates of the spatial-temporal mechanical behavior of the heart. These new capabilities will be used to answer the following fundamental questions of cardiac physiology: (3) What is the pattern of mechanical activation for different pacing sites on the ventricle? (4) How does the existence of an ischemic region alter this pattern of mechanical activation?. [(5) What is the mechanism by which pacing causes enhanced cardiac chamber function in hearts with dilated cardiomyopathy? This development in cardiac imaging methods will give us new tools to answer fundamental questions about ventricular function, such as the role of mechanical prestretch in causing arrhythmia, the effect of pacing lead placement on improving ventricular performance in the failing heart, and the redistribution of external work done by individual regions of the paced heart.]